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                                                                                                                                    【院长论坛】(4.4)Modulation of host functions by the Dot/Icm secretion system

                                                                                                                                    发布日期:2019-03-28    浏览次数:

                                                                                                                                    北京大学基础医学院

                                                                                                                                    院长论坛

                                                                                                                                     

                                                                                                                                    报告题目:Modulation of host functions by the Dot/Icm secretion system

                                                                                                                                     报  告  :Craig Roy, Ph.D.

                                                                                                                                                     Yale University School of Medicine

                                                                                                                                     时       间:2019 年4 月4 日(星期四)下午3:30

                                                                                                                                           点:生化楼三层中厅

                                                                                                                                    主  持  人:刘小云研究员

                                                                                                                                     

                                                                                                                                    报告简介:

                                                                                                                                    Bacterial pathogens must evade immune defenses to proliferate and persist within their hosts. Phagocytes play an important role in host defense by internalizing microbes and transporting them to lysosomes for degradation. Although most intracellular pathogens create vacuoles that evade fusion with lysosomes, Coxiella burnetii has the unique ability to survive and replicate inside of a lysosome-derived vacuole. Creation of this vacuole requires a bacterial Type IV secretion system called Dot/Icm. The C. burnetii Dot/Icm system transports over 100 different bacterial effector proteins into the host cell. Our research is focused on understanding how these bacterial effector proteins enable C. burnetii avoidance of host defense pathways. Several of these effector proteins manipulate host membrane transport pathways to create the lysosome-derived vacuole in which C. burnetii replicates. We have also identified a subset of effectors that disrupt the host response to infection. This lecture will focus on recent discoveries that demonstrate mechanisms by which these effectors function, and the mechanism of Dot/Icm secretion system function. 

                                                                                                                                     

                                                                                                                                    Representative Publications:

                                                                                                                                    1. Chetrit D, Hu B, Christie PJ, Roy CR, Liu J. (2018) A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. Nat. Microbiol.,3(6):678-686.

                                                                                                                                    2. Shames SR, Liu L, Havey JC, Schofield WB, Goodman AL, Roy CR. (2017) Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries. Proc Natl Acad Sci U S A., 114(48):E10446-E10454.

                                                                                                                                    3. Kohler LJ, Reed ShC, Sarraf SA, Arteaga DD, Newton HJ, Roy CR. (2016) Effector protein Cig2 decreases host tolerance of infection by directing constitutive fusion of autophagosomes with the Coxiella-containing vacuole. MBio, 7(4). pii: e01127-16.

                                                                                                                                    4. Choy A, Dancourt J, Mugo B, O'Connor TJ, Isberg RR, Melia TJ, Roy CR. (2012) The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science, 338:1072-6.

                                                                                                                                    5. Arasaki K, Toomre DK, Roy CR. (2012) TheLegionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion. Cell Host & Microbe, 11:46-57.

                                                                                                                                     

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